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Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
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Sexually Dimorphic Responses Reveal Multifaceted Benefits of Glibenclamide in Traumatic Brain Injury
Anupama Rani1, Sudhanshu P Raikwar1, Wonsuk Yoo1,2
1Department of Translational Neuroscience, Barrow Neurological Institute and St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Journal of Neurotrauma
|June 13, 2025
Summary
Glibenclamide (GLI) shows benefits for traumatic brain injury (TBI) in both sexes, improving cognitive and motor functions. However, GLI
Area of Science:
- Neuroscience
- Pharmacology
- Traumatology
Background:
- Sex disparities in traumatic brain injury (TBI) outcomes and neurodegeneration are not well understood.
- Males may be more susceptible to acute injury, while females are more vulnerable chronically.
- Understanding these differences is crucial for developing effective TBI therapies.
Purpose of the Study:
- To investigate the sex-specific effects of glibenclamide (GLI), a sulfonylurea-receptor 1 (SUR1) inhibitor, on multifaceted TBI outcomes.
- To evaluate GLI's impact on cognitive function, motor function, anxiety, neurodegeneration markers, neurogenesis, angiogenesis, and cerebral blood flow in a sex-specific manner.
Main Methods:
- 120 mice underwent controlled cortical impact (CCI) and were randomized to receive GLI or vehicle (DMSO) treatment.
- Treatment involved an initial intraperitoneal dose followed by a 7-day subcutaneous infusion.
- Outcomes assessed included behavioral tests (Morris water maze, rotarod, elevated plus maze), immunofluorescence for TAU, TDP43, SOX2, Ki67, VEGFA, and cerebral blood flow (CBF).
Main Results:
- GLI improved behavioral deficits in both sexes, with greater benefits observed in males.
- Sex-based differences were noted in motor impairment, anxiety, and chronic neurodegeneration markers (TAU, TDP43), with females showing sustained elevations.
- GLI downregulated TAU and TDP43, increased neurogenesis markers (SOX2) in females, and improved cerebral blood flow, particularly in males.
- Dimethyl sulfoxide (DMSO) alone showed benefits in females for TAU, TDP43, and CBF.
Conclusions:
- Novel sex-based differences in TBI response and GLI treatment efficacy were identified.
- Chronic TAU elevation in females presents a potential sex-specific therapeutic target.
- While GLI offers broad benefits, its effects are more pronounced in males, highlighting the need for sex-specific considerations in TBI clinical trial design and analysis.
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